Blood in the water: recent uses of zebrafish to study myeloid biology
Purpose of review
Myeloid cells contribute to immune response to infection and tissue regeneration after injury as well as to the developmental induction of the hematopoietic system overall. Here we review recent uses of zebrafish to advance the study of myeloid biology in development and disease.
Recent findings
Recent studies have made use of advanced imaging and genetic strategies and have highlighted key concepts in myeloid cell behavior. These include immune-cell cross-talk and subpopulation response in infection and regeneration, and tightly regulated inflammatory and tissue remodeling behaviors in develop...
Source: Current Opinion in Hematology - December 8, 2020 Category: Hematology Tags: MYELOID BIOLOGY: Edited by H. Leighton Grimes Source Type: research
Structural organization of the bone marrow and its role in hematopoiesis
Purpose of review
The bone marrow is the main site for hematopoiesis. It contains a unique microenvironment that provides niches that support self-renewal and differentiation of hematopoietic stem cells (HSC), multipotent progenitors (MPP), and lineage committed progenitors to produce the large number of blood cells required to sustain life. The bone marrow is notoriously difficult to image; because of this the anatomy of blood cell production -- and how local signals spatially organize hematopoiesis -- are not well defined. Here we review our current understanding of the spatial organization of the mouse bone marrow w...
Source: Current Opinion in Hematology - December 8, 2020 Category: Hematology Tags: MYELOID BIOLOGY: Edited by H. Leighton Grimes Source Type: research
Current understanding of human megakaryocytic-erythroid progenitors and their fate determinants
Purpose of review
This review focuses on our current understanding of fate decisions in bipotent megakaryocyte-erythroid progenitors (MEPs). Although extensive research has been carried out over decades, our understanding of how MEP commit to the erythroid versus megakaryocyte fate remains unclear.
Recent findings
We discuss the isolation of primary human MEP, and focus on gene expression patterns, epigenetics, transcription factors and extrinsic factors that have been implicated in MEP fate determination. We conclude with an overview of the open debates in the field of MEP biology.
Summary
Understanding ...
Source: Current Opinion in Hematology - December 8, 2020 Category: Hematology Tags: MYELOID BIOLOGY: Edited by H. Leighton Grimes Source Type: research
Systems analysis of hematopoiesis using single-cell lineage tracing
Purpose of review
In the last few decades, revolutionary advances in next-generation sequencing have led to single-cell lineage tracing technologies that now enable researchers to identify and quantify hematopoietic cell behavior with unprecedented detail. Combined readouts of cell lineage and cell state from the same cell mitigate the need to prospectively isolate populations of interest, and allow a system-level understanding of dynamic developmental processes. We will discuss the advantages and shortcomings of these technologies, the intriguing discoveries that stemmed from lineage tracing hematopoiesis at the singl...
Source: Current Opinion in Hematology - December 8, 2020 Category: Hematology Tags: MYELOID BIOLOGY: Edited by H. Leighton Grimes Source Type: research
A primer on single-cell genomics in myeloid biology
Purpose of review
Understanding the fast-moving field of single-cell technologies, as applied to myeloid biology, requires an appreciation of basic molecular, informatics, and biological concepts. Here, we highlight both key and recent articles to illustrate basic concepts for those new to molecular single-cell analyses in myeloid hematology.
Recent findings
Recent studies apply single-cell omics to discover novel cell populations, construct relationships between cell populations, reconfigure the organization of hematopoiesis, and study hematopoietic lineage tree and fate choices. Accompanying development of tec...
Source: Current Opinion in Hematology - December 8, 2020 Category: Hematology Tags: MYELOID BIOLOGY: Edited by H. Leighton Grimes Source Type: research
How haematopoiesis research became a fertile ground for regulatory network biology as pioneered by Eric Davidson
Purpose of review
This historical perspective reviews how work of Eric H. Davidson was a catalyst and exemplar for explaining haematopoietic cell fate determination through gene regulation.
Recent findings
Researchers studying blood and immune cells pioneered many of the early mechanistic investigations of mammalian gene regulatory processes. These efforts included the characterization of complex gene regulatory sequences exemplified by the globin and T-cell/B-cell receptor gene loci, as well as the identification of many key regulatory transcription factors through the fine mapping of chromosome translocation b...
Source: Current Opinion in Hematology - December 8, 2020 Category: Hematology Tags: MYELOID BIOLOGY: Edited by H. Leighton Grimes Source Type: research
Editorial introductions
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - December 8, 2020 Category: Hematology Tags: EDITORIAL INTRODUCTIONS Source Type: research
An update on the pathophysiology of immune thrombocytopenia
Conclusions
ITP is predominately a T cell disorder which leads to a breakdown in self tolerance mechanisms and allows for the generation of anti-platelet autoantibodies and T cells. Novel therapeutics that target T cells may be the most effective way to perhaps cure this disorder. (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - October 3, 2020 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Karina Yazdanbakhsh Source Type: research
Optimizing leukapheresis product yield and purity for blood cell-based gene and immune effector cell therapy
Purpose of review
A critical common step for blood-based ex-vivo gene and immune effector cell (IEC) therapies is the collection of target cells for further processing and manufacturing, often accomplished through a leukapheresis procedure to collect mononuclear cells (MNCs). The purpose of this review is to describe strategies to optimize the apheresis product cell yield and purity for gene and IEC therapies. Relevant data from the conventional bone marrow transplant literature is described where applicable.
Recent findings
Product yield is affected by three main factors: the peripheral blood concentration of the tar...
Source: Current Opinion in Hematology - October 3, 2020 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Karina Yazdanbakhsh Source Type: research
Role of complement in alloimmunization and hyperhemolysis
Purpose of review
The purpose of this review is to summarize the role of complement in regulating the removal of a target alloantigen following an incompatible red blood cell (RBC) transfusion, the formation of alloantibodies following RBC alloantigen exposure, and the development of hyperhemolysis in patients with sickle cell disease (SCD).
Recent findings
Recent studies demonstrate that complement can accelerate alloantibody-mediated removal of target alloantigens from the RBC surface following incompatible transfusion. Complement also influences alloantigen availability during developing alloimmune responses and se...
Source: Current Opinion in Hematology - October 3, 2020 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Karina Yazdanbakhsh Source Type: research
Human babesiosis: recent advances and future challenges
Purpose of review
As human babesiosis caused by apicomplexan parasites of the Babesia genus is associated with transfusion-transmitted illness and relapsing disease in immunosuppressed populations, it is important to report novel findings relating to parasite biology that may be responsible for such pathology. Blood screening tools recently licensed by the FDA are also described to allow understanding of their impact on keeping the blood supply well tolerated.
Recent findings
Reports of tick-borne cases within new geographical regions such as the Pacific Northwest of the USA, through Eastern Europe and into China are ...
Source: Current Opinion in Hematology - October 3, 2020 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Karina Yazdanbakhsh Source Type: research
New insights into IVIg mechanisms and alternatives in autoimmune and inflammatory diseases
Purpose of review
Intravenous immunoglobulin (IVIg) is an effective treatment for an increasing number of autoimmune and inflammatory conditions. However, IVIg continues to be limited by problems of potential shortages and cost. A number of mechanisms have been described for IVIg, which have been captured in newly emergent IVIg mimetic and IVIg alternative therapies. This review discusses the recent developments in IVIg mimetics and alternatives.
Recent findings
Newly emergent IVIg mimetics and alternatives capture major proposed mechanisms of IVIg, including FcγR blockade, FcRn inhibition, complement inhibition, imm...
Source: Current Opinion in Hematology - October 3, 2020 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Karina Yazdanbakhsh Source Type: research
Update on the pathophysiology of transfusion-related acute lung injury
Purpose of review
The aim of this study was to discuss recent advances regarding the pathogenesis of transfusion-related acute lung injury (TRALI), which highlight the pathogenic role of macrophages.
Recent findings
TRALI remains a leading cause of transfusion-related fatalities, despite the success of the mitigation strategy, and therapeutic approaches are unavailable. Neutrophils (PMNs) are recognized pathogenic cells in TRALI. Macrophages have previously also been suggested to be pathogenic in mice via binding of C5a to their C5a-receptor, producing reactive oxygen species (ROS), which damages the pulmonary endothe...
Source: Current Opinion in Hematology - October 3, 2020 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Karina Yazdanbakhsh Source Type: research
Platelet transfusion for patients with platelet dysfunction: effectiveness, mechanisms, and unanswered questions
Purpose of review
In this review, we discuss current clinical guidelines and potential underlying mechanisms regarding platelet transfusion therapy in patients at risk of bleeding, comparing management of patients with thrombocytopenia versus those with qualitative platelet disorders.
Recent findings
Platelet transfusion therapy is highly effective in managing bleeding in patients with hypoproliferative thrombocytopenia. Clinical trials have demonstrated that platelet transfusion can be used at a lower trigger threshold and reduced platelet doses, and may be used therapeutically rather than prophylactically in some si...
Source: Current Opinion in Hematology - October 3, 2020 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Karina Yazdanbakhsh Source Type: research
Advances in chimeric antigen receptor T cells
Purpose of review
To discuss the important advances in CAR T cell therapy over the past year, focusing on clinical results where available.
Recent findings
Approximately 30 years after they were first conceived of and 15 years after the first small-scale single-center clinical trials, the past 3 years represent a major milestone in the development of CAR T cells. In the United States, the Food and Drug Administration (FDA) approved Tisagenlecleucel for the treatment of relapsed/refractory B-ALL and Axicabtagene Ciloleucel, for adults with relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) in 2017. Tisagenle...
Source: Current Opinion in Hematology - October 3, 2020 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by Pavan Reddy Source Type: research
